African-American men have the highest incidence of prostate cancer of any ethnic subgroup of the world's population. In recent years, there has been a dramatic increase in the annual rate of prostate cancer. A number of possible explanations for this increased incidence are being actively explored including dietary, hormonal, and genetic factors. It is well known that the familial component is a strong risk factor for prostate cancer. The genetic studies performed to date (on mostly Caucasian families) suggest that multiple genes are involved in prostate cancer susceptibility in Caucasian families (i.e., genetic risk factors may differ among the families). While several possible locations for prostate cancer genes have been suggested, all but one of those genes have not been definitely identified and sequenced. So far, there are not enough data collected on African-American families to determine whether these suggested genes, reported in Caucasian families, are also important for African-Americans. The purpose of this proposed study is to collect high-risk African-American families with a strong family history of prostate cancer which will be used (1) to determine whether prostate cancer risk in this particular population is likely to be due to genes in the same or different regions than in Caucasians and (2) to help definitively locate and identify these genes. We plan to look at the candidate regions to identify families linked to the candidate loci and eventually perform a genomic scan in unlinked families to look for any new susceptibility loci, which may contribute to the high incidence rate of prostate cancer in African-Americans. This study may show that prostate cancer in African-American men is attributable to a different set of genes than in Caucasian Americans. Alternatively, the same genes may be important in both populations, but with a higher frequency of the disease-causing form of the gene in the African-American population. The detection of susceptibility to existing genetic loci or new genetic loci in conjunction with modern prostate cancer screening procedures will improve the detection and diagnosis of this cancer at an earlier age and will help immensely to alleviate the elevated disease risk in this population.